MicroRNA induction of cardiac regeneration

Abstract

The invention relates to compostions and methods for promoting cellular proliferation and de-differentiation of cells into stem cells to foster tissue regeneration. Specifically, the invention relates to transiently administering a microRNA (miR) or its mimic for promoting cardiomyocyte proliferation and cardiac regeneration.

What is claimed is: 
     
       1. A method for promoting cardiac repair and regeneration in a subject, the method comprising: transiently administering locally to the heart of said subject a composition comprising a microRNA (miR) 302-367 cluster or a miR 302-367 cluster mimic, wherein said transient administration is sufficient to transiently activate cardiomyocyte proliferation, but not to persistently reactivate the cell cycle of postnatal cardiomyocytes. 
     
     
       2. The method of  claim 1 , wherein the transient administration comprises a single administration of the composition to the subject. 
     
     
       3. The method of  claim 1 , wherein the composition comprises valproic acid. 
     
     
       4. The method of  claim 1 , wherein said miR is operably linked to a regulatory sequence. 
     
     
       5. The method of  claim 4 , wherein said regulatory sequence is an inducible promoter. 
     
     
       6. The method of  claim 5 , wherein said inducible promoter is a doxycycline inducible promoter. 
     
     
       7. The method of  claim 1 , wherein said miR is encoded by a nucleic acid sequence present within a vector. 
     
     
       8. The method of  claim 7 , wherein the vector is a viral vector. 
     
     
       9. The method of  claim 8 , wherein the viral vector is a lentivirus vector. 
     
     
       10. The method of  claim 7 , wherein the vector is a plasmid vector. 
     
     
       11. A method for promoting cardiac repair and regeneration in a subject, the method comprising: transiently administering locally to the heart of said subject a composition comprising a microRNA (miR) cluster or its mimic, wherein said cluster comprises one or more of miR302b and miR302c or two or more of miR302b, miR302c, and miR367, and wherein said transient administration is sufficient to transiently activate cardiomyocyte proliferation, but not to persistently reactivate the cell cycle of postnatal cardiomyocytes. 
     
     
       12. A method for promoting cardiac repair and regeneration in a subject, the method comprising: transiently administering intravenously at least once daily for 7 days said subject a composition comprising a microRNA (miR) 302-367 cluster or a miR 302-367 cluster mimic, wherein said transient administration is sufficient to transiently activate cardiomyocyte proliferation, but not to persistently reactivate the cell cycle of postnatal cardiomyocytes. 
     
     
       13. A method for promoting cardiac repair and regeneration in a subject, the method comprising: transiently administering intravenously at least once daily for 7 days said subject a composition comprising a microRNA (miR) cluster or its mimic, wherein said cluster comprises one or more of miR302b and miR302c or two or more of miR302b, miR302c, and miR367, and wherein said transient administration is sufficient to transiently activate cardiomyocyte proliferation, but not to persistently reactivate the cell cycle of postnatal cardiomyocytes.